Is our genome a straitjacket or a comfy sweater?

We can't know how significant epigenetics is until scientists define it.

NEW YORK CITY, NY—Back in December, the geneticist Mary Claire King warned that, when it comes to epigenetics, "we have a semantic problem that's becoming a philosophical problem—and on the verge of becoming a dangerous political one." She meant that scientists themselves were being a bit sloppy with defining epigenetics, the process by which long-term biological changes can occur without changes in the underlying DNA. This sloppiness is now leading to public confusion about what exactly is involved in epigenetics and how it might affect human health and behavior. In the absence of clear ideas, non-scientists are grasping at any meaning they find convenient and using that to draw grand conclusions about human nature.

Unfortunately, nearly every aspect of this confusion was on display at a panel called "The Social Impact of Epigenetics," part of this past weekend's World Science Festival in New York. The panel started with grand declarations about how Lamarck might have been on to something about the inheritance of acquired characteristics. But before it was over, one panelist was saying that we only have a single clear example of this in mammals, and it involves coat color in mice.

What is epigenetics anyway?

We partly described epigenetics when we covered a recent example that suggested it may influence human metabolism. But it's worth going over in a bit more detail. In short, epigenetics involves stable changes in gene activity that don't involve changes in the DNA.

Almost all human cells share an identical collection of DNA. The difference between cells comes down to which genes they activate and how strongly they activate them. Some of these differences in gene activity are transient as cells respond to their environmental conditions. Others are more permanent, so that once a cell adopts a neural or blood identity it maintains that identity. It's these more permanent changes that are often referred to as epigenetic since they get passed on to a cell's daughters when it divides.

The differences in gene activity are mediated by a combination of proteins that stick to the DNA, and some of these stick to specific sequences. For example, there's a protein called REST that binds a sequence near many genes involved in nerve functions and shuts them off in any cell that isn't a neuron. Other proteins called histones stick to DNA more generally, helping package it up so that it fits inside a cell. Histones can be chemically modified in ways that make the nearby genes either more or less active.

One source of confusion is that both the transient and more permanent responses often involve the same proteins and histones. Because of this, some people (including Jim Watson) have argued that none of this should be considered epigenetics—it's all just gene regulation. In contrast, some people on the panel were saying that even the transient changes constitute epigenetic activity and that epigenetic markings change almost daily (although the panel was hardly unanimous on this).

Daily changes in epigenetic programs probably sound new and exciting. But if things are defined this broadly, then epigenetics is not as exciting as it seems. It's just another way of saying that gene activity changes in response to the environment, which was already firmly established.

Epigenetics across generations

As noted above, these sorts of epigenetic changes only apply when a cell divides; they don't generally get inherited by a fertilized egg. In fact, part of the process of producing sperm and eggs involves wiping out most of this information in its entirety. But there is a form of epigenetic inheritance that can survive this. Some specific DNA sequences can be chemically modified by having an extra carbon added to one of the bases in a process called methylation. Methylation often survives through the production of sperm and eggs and on through fertilization—and in some cases through much of the life of the organism. In contrast to the modifications that can change daily, methylation only seems to change very slowly over the course of an organism's lifespan.

If methylation in the sperm and eggs can be altered in response to environmental conditions, then it's possible for a parent's environment to influence gene expression in their children. There is clear evidence that this sort of epigenetic inheritance goes on in plants and some insects. But, when it comes to humans, the only evidence we have so far is suggestive. When the panel was asked about cases that went beyond a maternal influence on one generation of offspring, biologist Randy Jirtle said there's only a single well-demonstrated case in mammals and it involves coat coloration in mice.

So even though epigenetic inheritance may end up being significant, it's hardly an earth-shattering change in our understanding of human heredity. In fact, there was nothing that came up during the discussion that justified mentioning Lamarck's name.

Scientific sloppiness and public confusion

The person who did mention Lamarck, moderator Bill Blakemore, probably should have known better. At one point during the program, he admitted that when talking to scientists about the topic he never came across the same definition twice. That sort of confusion was present throughout the discussion, as different scientists lumped everything from transient changes in gene expression to trans-generational inheritance under the "epigenetics" umbrella without bothering to clarify what it was they were talking about.

All of this, of course, would just be an obscure academic debate if people weren't trying to infer something about human nature from the existence of epigenetics. The title of the panel itself, "The Social Impact of Epigenetics," implies that the discovery of human epigenetics will have an impact on how we run our society. Lone Frank, a European journalist on the panel, was explicit about how epigenetics changed her perspective. She called genetic determinism, the idea that your genes dictate who you are, a "straightjacket." For her, the chance that epigenetics meant that the genes could be overridden made the genome seem more like a "comfy sweater."

This was an attitude similar to the one the President of the European Research Council expressed in Stockholm. In general, people seem to be hopeful that epigenetics can explain some persistent social issues without forcing us to accept that these issues are all in our genes and there's nothing we can do. Given how little we know about human epigenetics, hope seems very premature.

In any case, the rest of the panel was there to put a brake on things. Jean-Pierre Issa pointed out that some genes are deterministic and many others will increase risks no matter what epigenetic inheritance does to them. At best, in his view, epigenetics will only shift things like disease risks a few percentage points; it won't completely reset your biology. And when it comes to human health, you could make a larger impact simply by following basic health advice: eat well, exercise, and avoid smoking. (Naturally, someone on the panel suggested these good habits could change your epigenetic status.)

Could our understanding of epigenetics create or solve societal issues? Absolutely. Some aspects of cancer seem to involve epigenetic changes, and epigenetics may explain why some childhood traumas cause changes that persist into adulthood. But the same could be said of plain old vanilla genetics. In the same way, the thorny questions considered by the panel—do we have a right to epigenetic privacy? Should we do something about those we find are epigenetically at risk of violence? These are things genetics itself has forced us to look at previously (and we didn't always come up with satisfying answers then).

But right now, all of that speculation is extremely premature. Scientists themselves are still arguing over what is and is not an epigenetic change. They're still struggling to provide conclusive evidence about how significant it is in humans. Until we have a clearer picture of that, asking what its impact on society might be isn't likely to generate any informative answers.

I think Ars is overblowing the significance of epigenetics. Phenotype is not determined just through gene sequence and epigenetics. Epigenetic's effect on phenotypic variation between human beings is probably marginal at best.

She called genetic determinism, the idea that your genes dictate who you are, a "straightjacket." For her, the chance that epigenetics meant that the genes could be overridden made the genome seem more like a "comfy sweater."

You don't need epigenetics to make it a comfy sweater. All you need are interactions between genes, the environment, and ideally actions you take (e.g. exercise, education). I think those interactions are sufficiently well demonstrated without epigenetics.

Some genes are a bit of a straitjacket. Eye and hair color, for example. There aren't that many determinants, and they have a strong effect. You can still wriggle your way out if you really want (contacts, dye). Most genes implicated in behavior have much, much weaker effects....

I think Ars is overblowing the significance of epigenetics. Phenotype is not determined just through gene sequence and epigenetics. Epigenetic's effect on phenotypic variation between human beings is probably marginal at best.

Unless I'm mistaken, the excitement over epigenetics has no bearing on phenotypic variance, but in non-visible behavioral, disease, or health issues such as diabetes, cancer, etc.

An important addition to this discussion is the recognition that (in theory) every cell in your body shares the same genome, but there is no reason to believe that epigenetic changes must be identical from cell to cell. Thats provides a great deal more opportunity for complicated variation. Hence, less strait.

In general, people seem to be hopeful that epigenetics can explain some persistent social issues without forcing us to accept that these issues are all in our genes and there's nothing we can do.

What are some of the social issues they are talking about?

Homosexuality has been suggested to be epigenetic.

Yes, I was surprised to see no mention of it in this article. Homosexuality caused by an epigenetic marker inherited from the parent of the opposed sex is actually the best explanation that makes sense to me, and it is indeed an important social issue that should have been at least mentioned here.

I am also surprised not to have seen any additional papers on the subject: It is almost a revolutionary concept and explains both the general manner in which homosexuality happens and also the anomalies about twins and siblings, for instance. I would have thought that the "born this way" proponents would fund more similar studies to confirm or debunk the (peer-reviewed) paper, if only to shut off the homophobes for good.

The paper was released only last year though (reported by Ars too), so maybe it is too recent for follow-ups.

Fear cuts both ways. Not everyone would be accepting of the idea that homosexuality can be cured.

Well it's not a disease, so a cure is irrelevant. But if you mean sexual orientation can be changed, I don't think it's possible, since this happens upon conception in some rare cases. It's not like the same father always has gay kids. Well, except for my dad! You can't fix the father's sperm either, you can't fix the fetus because the epimarker is now replicated to every cell, and eventually the human body grows trillions of them.

Plus, the homophobes are usually the same crowd that is all "love the sinner, hate the sin" and anti-abortion, so I don't see they have any choice when the doctor tells them: I have two news for you, the good news is that your son will be gay, the bad news is that the closest church that does not consider gays as vicious beasts is 200 miles away."

Fear cuts both ways. Not everyone would be accepting of the idea that homosexuality can be cured.

Well it's not a disease, so a cure is irrelevant. But if you mean sexual orientation can be changed, I don't think it's possible, since this happens upon conception in some rare cases. It's not like the same father always has gay kids. Well, except for my dad! You can't fix the father's sperm either, you can't fix the fetus because the epimarker is now replicated to every cell, and eventually the human body grows trillions of them.

Plus, the homophobes are usually the same crowd that is all "love the sinner, hate the sin" and anti-abortion, so I don't see they have any choice when the doctor tells them: I have two news for you, the good news is that your son will be gay, the bad news is that the closest church that does not consider gays as vicious beasts is 200 miles away."

The question would be more like: is homosexuality inheritable, or born homosexual due to the brain malfunction? I believe homosexuality is some sort of an after birth behavior genetic "problem" its occurrence to that person in his much later days, or something went haywired somewhere along that line after that person has grown up and he has introduced by a third party a gay man what an orgasm is. (exemple: Some gay guys would tell this heterosexual under age little kid he is handsome, smart, nice person that he is everything, in attempt to have sex with him. Question to the gays, was this how you have suduced the non gays?)

Behavior can't be changed or cured even he's got locked up in a cage and had beaten to half dead. How do you change own behaviour? It just impossible to do so. Ask yourself this, can you change? Ones behavior stick to his lifespan. But if it is curable as someday by genetical engineering the process could be also reversible and make all hetrosexuals turned into homosexuals. Not by will, though.

Err, people are gay even before exhibiting any gay behavior, which is a concept that does not exist anyway. Is that still the "lifestyle" thing? And assimilating gays to pedos or having brain malfunctions, real educated and a great way to have nobody care about what you "believe".

Well the whole paper reads like a "we don't really know" so I wouldn't get too far ahead hanging anything onto it.

Right, but it's been peer reviewed too, and it follows previous research by the same team from years ago, so it's not something they pulled out of thin air either. The results presented are the only ones that make sense so far. We knew already from previous studies that there was some sort of genetic link, but not quite genetic either because of some unexplained anomalies, that epigenetic marker explain a lot of things. No doubt it isn't a perfect explanation, after all, it is the ONLY study that shows such a relationship so far, that's why I was hoping other scientists would work on it and develop their findings. I think it is a discovery.

our DNA starts us in a certain position, the universe does various things with/to us, and we have a bit of ability to nudge things one way or another.

the postman rolls by here around 2-3 every day. i recognize the sound of the post truck's diesel. a day is 24 hours. people put up lights at christmas. i think this is partly because winter is dark and depressing, and we need something to lighten the mood....

point being, the universe has rhythms and patterns, and human culture has added its own on top of that. an individual is somewhat like a jellyfish in the ocean current. if you think of the human soul/consciousness/etc as being like a network stack, i think that's a decent analogy. DNA is the ethernet hardware, gene expression is the data link layer, the rhythms of the universe are the internet layer, human culture is the transport layer, and you are the application.

however, this is all just the idle observation of someone who prefers top-down analysis and knows jack squat about molecular biology.

For some reason the comments always end up with questions about curing the gays. What if the cure goes both ways? Would the heteros be interested in such thing?

My suggestion is to leave the scientific speculations to the scientists.

sexuality is horribly misunderstood. there are all sorts of varying social rules about what's appropriate in the bedroom; what you can say aloud. what's appropriate science in one culture (even within the US) might offend another, hindering collaboration. strong feelings and ignorance are a potent combination. the war on janet jackson's single exposed nipple: the most destructive force threatening america!

how can you attempt to introduce logic to a situation like that and expect it to sink in? before science can properly sort out sexuality, sexial orientation, and so on, society has to gain some mutual goddamn tolerance for individual differences. until then, it's just trying to piss in a rainstorm.

For some reason the comments always end up with questions about curing the gays. What if the cure goes both ways? Would the heteros be interested in such thing?

My suggestion is to leave the scientific speculations to the scientists.

Speculation at this point is "I don't know" so that's not very helpful. Anyway my point is about "fear" not a "cure". Unless one's science is picking a particular conclusion, then looking for supporting evidence, any science we do do will have the potential to go in ways the audience may not desire. The comment I responded to was speculating that further research should be done to prove the homophobes wrong. Who's going to fund that? The homophobes?

When the panel was asked about cases that went beyond a maternal influence on one generation of offspring, biologist Randy Jirtle said there's only a single well-demonstrated case in mammals, and it involves coat coloration in mice.

I'm guessing that by "well-demonstrated case" they meant RCT so you're not going to find human studies in that camp. It should be noted that that study, showing that, for mice, maternal diet changed phenotype expression in offspring, is already 15 years old:

But the other significant study of note that I'm aware of is the "Overkalix study" which does support transgenerational epigenetic effects in humans (both grandmothers and grandfathers affecting grandchildren, ie "beyond maternal influence"):

In general, people seem to be hopeful that epigenetics can explain some persistent social issues without forcing us to accept that these issues are all in our genes and there's nothing we can do.

What are some of the social issues they are talking about?

Homosexuality has been suggested to be epigenetic.

If that were the case, you would think that it would be self correcting in it's potential lack of propagation.

What I don't understand is (and this is from health class many many moons ago...) since a woman's ovum are essentially generated and fixed at birth, how these changes would even occur. I can potentially understand that some chemicals in the body could force cells to turn on/off certain gene patterns, but I am fairly skeptical that this happens.